首页|Medicinal chemistry strategies towards the development of non-covalent SARS-CoV-2 Mpro inhibitors

Medicinal chemistry strategies towards the development of non-covalent SARS-CoV-2 Mpro inhibitors

扫码查看
原文链接
  • 万方数据
  • 维普
The main protease(Mpro)of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle.The covalent Mpro inhibitor nirmatrelvir(in combination with ritonavir,a pharmacokinetic enhancer)and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use.Effective antiviral drugs are needed to fight the pandemic,while non-covalent Mpro inhibitors could be promising alternatives due to their high selectivity and favorable druggability.Numerous non-covalent Mpro inhibitors with desirable properties have been developed based on available crystal structures of Mpro.In this article,we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent Mpro inhibitors,followed by a general overview and critical analysis of the available information.Prospective viewpoints and insights into current strategies for the development of non-covalent Mpro inhibitors are also discussed.

COVID-19SARS-CoV-2Main proteaseNon-covalent inhibitorsMedicinal chemistry strategies

Letian Song、Shenghua Gao、Bing Ye、Mianling Yang、Yusen Cheng、Dongwei Kang、Fan Yi、Jin-Peng Sun、Luis Menéndez-Arias、Johan Neyts、Xinyong Liu、Peng Zhan

展开 >

Department of Medicinal Chemistry,Key Laboratory of Chemical Biology(Ministry of Education),School of Pharmaceutical Sciences,Cheeloo College of Medicine,Shandong University,Jinan 250012,China

Shenzhen Research Institute of Shandong University,Shenzhen 518057,China

The Key Laboratory of Infection and Immunity of Shandong Province,Department of Pharmacology,School of Basic Medical Sciences,Shandong University,Jinan 250012,China

Key Laboratory Experimental Teratology of the Ministry of Education,Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Cheeloo College of Medicine,Shandong University,Jinan 250012,China

Centro de Biolog(i)a Molecular"Severo Ochoa"(Consejo Superior de Investigaciones Cient(i)ficas&Autonomous University of Madrid),Madrid 28049,Spain

KU Leuven,Department of Microbiology and Immunology,Rega Institute for Medical Research,Laboratory of Virology and Chemotherapy,Leuven 3000,Belgium

展开 >

Major Basic Research Project of Shandong Provincial Natural Science FoundationScience Foundation for Outstanding Young Scholars of Shandong ProvinceForeign Cultural and Educational Experts ProjectGuangdong Basic and Applied Basic Research Foundation中国博士后科学基金Ministry of Science and Innovation of Spain through grant

ZR2021ZD17ZR2020JQ31GXL202000150012021A15151107402021M702003PID2019-104176RB-I00/AEI/10.13039/501100011033

2024

10.1016/j.apsb.2023.08.004

药学学报(英文版)

药学学报(英文版)

CSTPCD
ISSN：
年,卷(期)：2024.14(1)
  • 148